Salt sensitivity is defined as a quantitative trait in which an increase in sodium (Na+) load leads to an increase in blood pressure (BP). While universal consensus does not exist on the exact quantity of the Na+ load, magnitude of the pressure increase or the specific protocol details required for this designation, the presence of salt sensitivity is clearly associated with an increased prevalence of cardiovascular events and mortality, irrespective of unchallenged BP levels. Indeed, normotensive (NT), yet salt-sensitive (SS) individuals have a cumulative mortality rate similar to that of hypertensive (HT) patients. In addition, SS individuals, even those with normal BP levels when initially studied, have a greater age-related increase in BP. Overall, salt sensitivity has been estimated to be present in 51% of hypertensive and 26% of normotensive subjects, posing a major public health problem in the United States and other Westernized societies.
The underlying pathophysiological mechanisms of salt sensitivity are currently unknown. However, there is strong evidence that genetic mechanisms may underlie variations in the BP response to dietary salt intake. In particular, there is tight maternal-offspring association of BP change with dietary Na+ restriction. Salt sensitivity, hypertension and related cardiovascular diseases are thought to result from the interaction of genes with the environment (e.g., stress and diet), but the specific genes involved in susceptibility to salt sensitivity have not been completely clarified.
The Na+-bicarbonate co-transporter gene (SLC4A5) on chromosome 2 encodes a protein that transports Na+ and HCO3− electrogenically across the basolateral membranes of many cell types, including renal tubule cells, into the interstitial fluid and ultimately into the circulation. SNPs of SLC4A5 have been associated with baseline and 10-year follow-up BP in previous studies. Additionally, targeted mutation of SLC4A5 has been found to induce arterial hypertension in mice (Groger et al., 2012).
There is a long felt need in the art for compositions and methods useful for identifying, diagnosing, treating, and monitoring subjects with salt sensitivity of blood pressure. The present invention satisfies these needs.